It is also possible that neurons

derived from VZ versus OSVZ radial glia are indistinguishable, with a neuron’s timing of origin and migration to the cortical plate being the main determinant of what subtype it will become. Whether oRG cells give rise to distinct neuron subtypes or simply represent a cellular means to amplify neurogenesis is a pivotal question with obvious ramifications for producing specific subtypes of cortical neurons in vitro from human pluripotent stem cells. If we assume that having the correct type of progenitor cell is important for producing neurons of a desired subtype, then this introduces a new challenge for producing excitatory neurons of upper cortical layers from hESCs. As mentioned earlier, upper-layer neurons

may be particularly involved in human diseases of cognitive function including dementia, retardation, schizophrenia, Osimertinib chemical structure and autism. The ability to generate cells with the correct upper-layer identity may be required in order to study the pathophysiology of these disorders. The oRG cells from which most human upper-layer neurons originate represent a new target cell type for hESC derivation. Researchers commonly selleck chemicals use the presence of neural rosettes in differentiating cell cultures as an indication that neural stem cells with properties of neuroepithelial/radial glial cells are abundant and actively producing neurons. In ventricular RG cells, the polarity protein Par3 and the engagement of N-cadherin at apical junctions are required to promote

Notch and β-catenin signaling, respectively, and thus maintain progenitor status (Bultje et al., 2009 and Zhang et al., 2010). Thus, apical-basal polarity is an essential property by which neuroepithelial cells comprise a self-supportive niche that does not require distinct supporting cells. The self-organization of dissociated, differentiating ESCs into a polarized neuroepithelium attests Ergoloid to the intrinsic value of cell-cell interactions for neural stem cell maintenance (Eiraku et al., 2008). Lacking cell-cell interactions of this type, what are the mechanisms by which oRG cells persist in the OSVZ? We presume that there are compensatory mechanisms in the OSVZ that activate some of the same intracellular signaling pathways through alternate means to prevent oRG cell differentiation. The basal fibers of oRG cells are probably critical for receiving signals from the environment that restrain differentiation, induce proliferation, and promote survival. We demonstrated that Notch signaling is required for oRG cell maintenance (Hansen et al., 2010), although why apical polarity is not required for this pathway in oRG cells as it is in ventricular RG is unknown. Integrin binding is also required to maintain Pax6+ OSVZ progenitor cells (Fietz et al., 2010).

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